Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression. |
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Authors: | Catalina Lopez de Lara Jelena Brezo Guy Rouleau Alain Lesage Mimi Dumont Martin Alda Chawki Benkelfat Gustavo Turecki |
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Institution: | McGill Group for Suicide Studies, Douglas Hospital Research Center, Montreal, Canada. |
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Abstract: | BACKGROUND: Suicide and depressive disorders are strongly associated, yet not all depressed patients commit suicide. Genetic factors may partly explain this difference. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene and its 5' upstream region may predispose to suicide in major depressive disorder (MDD) and whether this predisposition is mediated by impulsive-aggressive behaviors (IABs). METHODS: We genotyped 14 single nucleotide polymorphisms (SNPs) in 259 depressed subjects, 114 of which committed suicide while depressed. Phenotypic assessments were carried out by means of proxy-based interviews. Single-marker and haplotype association analyses were conducted. Differences in behavioral and personality traits according to genotypic variation were investigated, as well as genetic and clinical predictors of suicide. RESULTS: We found two upstream and two intronic SNPs associated with suicide. No direct effect of these variants was observed on IABs. However, a slight association with reward dependence scores was found. Controlling for suicide risk factors, two SNPs (rs4448731 and rs4641527) significantly predicted suicide, along with cluster B personality disorders and family history of suicide. CONCLUSIONS: The TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in MDD; however, our findings do not support the role of IABs as mediators. |
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Keywords: | Aggressive-impulsive behavior genetic predisposition major depressive disorder single nucleotide polymorphisms suicide tryptophan hydroxylase-2 |
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